Muscle stiffness is a common symptom for which no specific etiology has been determined and no treatment exists as of yet. Muscle stiffness often occurs from lack of movement, for example after prolonged bed rest (Clavet et al., 2008, CMAJ, March 11, 178(6):691-7), in the elderly (Trindade et al., 2012, J Biomech., January 3, 45(1):199-201; Wojtysiak, 2013, Folia Biol (Krakow), 61(3-4):221-6, PubMed PMID: 24279172), with paralysis of limbs due to neurological or muscular diseases, due to metabolic conditions such as diabetes (Duffin, 2002, Diabet Med. December, 19(12):1009-13, PubMed PMID: 12647842), and after excessive exercises such as running a marathon etc. The severity of muscle stiffness can range from an uncomfortable sensation of rigidity to exacerbation of spasticity (if there is a previous central nervous system injury). Both rigidity and spasticity may be accompanied by non-specific pain. The high incidence of muscle stiffness represents an enormous cost to society worldwide.
Spasticity commonly presents as muscle over-activity, reduction in the ability to relax specific muscles, hypertonia, paresis, muscle spasms, and loss of fine motor control, attributed to neural mechanisms. However, less understood symptoms of spasticity include increased stiffness in the soft tissue, muscle fatigue, and postural changes in the limbs, which can be explained by non-neural/peripheral contributions that have secondary effects on skeletal muscles. In fact it has been shown that spasticity is not an immediate consequence of CNS injury as it progresses during the weeks and months after injury; this suggests that there are other non-neural/peripheral factors that contribute to spasticity (Lundstrom et al., 2008, Eur J Neurol., 15(6):533-9).
Surgical, pharmacological, and physiotherapy techniques are among the most common interventions offered to alleviate spasticity. Pharmacological agents include oral medication such as benzodiazepines, baclofen, tizanidine hydrochloride, and dantrolene. Diazepam is one of the oldest and most commonly used benzodiazepine for treating spasticity. Botulinum toxin type A is used for focal treatment of overly spastic muscles, while intrathecal baclofen is commonly used to reduce spasticity in individuals with spinal cord injury. However, even though current pharmacological agents significantly reduce spasticity, their use does not always translate into increased function because of side effects including drowsiness and muscle weakness (Nielsen et al., 2007, Acta Physiol (Oxf), February, 189(2):171-80).